Project Summary Stroke is the 5th leading cause of death and number one cause of adult disability in the United States. The primary goal of ischemic stroke treatment is quickly restoring blood perfusion. However, studies have shown that this return of blood flow, while necessary, can also cause damage to local tissue. Hypothermia has been shown to decrease this ?reperfusion injury?. The overall goal of our research is to couple therapeutic hypothermia to intracranial thrombectomy devices called stentrievers or stent retrievers. Our device is a patented tissue cooling system that rapidly cools ischemic tissue at risk of reperfusion injury. Our Phase I work will demonstrate 1) ease of use and cooling effectiveness feasibility with a human-scaled prototype, 2) rapid brain cooling during and after occlusion and 3) brain tissue salvage and neurological benefit in a canine occlusion model. Phase II will refine the design and prepare the technology for first-in-man studies. Specific Aims: 1.) Demonstrate ease of use and cooling effectiveness of FocalCool's CoolGuide? cooling system with stent retrievers, characterizing the cooling performance and ensuring safe operation in vitro. 2.) Translate the human-scaled prototype to a canine-scaled version for in vivo testing. 3.) Demonstrate safe cooling before and during reperfusion, yielding infarct volume reduction and improved neurological outcome. Cooling capability and stent retriever device integration will be determined using our in vitro circulatory system model. To demonstrate the safety, performance, and efficacy of rapid localized brain tissue cooling, in vivo studies will be conducted using an in vivo model of transient ischemic stroke. Metrics of safety will include a decrease in core temperature no larger than 1.0C and safe maintenance of blood pressures and systemic hemodynamics during cooling. Metrics for performance will include device ease of use with stent retrievers and tissue temperature reduction in at-risk brain tissue regions during and after occlusion. Metrics of efficacy will include reduction in infarct volume and neurological improvement compared to controls. Relevance: Effective recanalization with today's stent retrievers is a promising new standard of care for ischemic strokes. Reperfusion injury however, following recanalization continues to be an unmet problem in ischemic stroke care. Approximately 50% of stent retriever patients leave with modified Rankin Scores greater than 3, indicating moderate disability to severe disability, including death. The technological innovation of combining stroke treatment therapies ? mechanical thrombectomy and precise well-integrated reperfusion hypothermia ? may yield synergistic benefits, resulting in reduced infarct size and improved long-term neurological outcomes. Both Medtronic and Stryker support this work (Please see letters of Support).